Sepsis Regimens Differ in 90-Day Risk of Death

Action Points

Explain that patients with severe sepsis were more likely to die within 90 days if they received hydroxyethyl starch solution rather than Ringer's acetate.

Note that those receiving starch solution were also more likely to require renal-replacement therapy.

For patients with severe sepsis, fluid resuscitation with Ringer's acetate was safer than it was with a widely used solution of hydroxyethyl starch, researchers reported.

In a randomized blinded trial, patients treated with hydroxyethyl starch 130/0.42 had an increased risk of death at 90 days, compared with those given Ringer's acetate, according to Anders Perner, MD, of the Rigshospitalet in Copenhagen, and colleagues.

They were also more likely to need renal-replacement therapy during the course of treatment, Perner and colleagues reported online in the New England Journal of Medicine.

High-molecular weight hydroxyethyl starch, a colloid, has been shown in two randomized trials to increase the risk of acute kidney failure in patients with severe sepsis, Perner and colleagues noted.

But in those trials, the solution used had a molecular weight of 200 kiloDalton and a substitution number of more than 0.42, while a potentially less dangerous version, with a molecular weight of 130 kD and a substitution number of 0.42, remains widely used in intensive care units.

To examine the safety of the lower molecular-weight solution, Perner and colleagues studied outcomes in 798 sepsis patients randomly assigned to either Ringer's acetate, a crystalloid, or to hydroxyethyl starch 130/0.42.

The primary outcome of the study was death or reliance on dialysis after 90 days, but the researchers also analyzed several other factors, including severe bleeding and the need for renal-replacement therapy during treatment.

By 90 days after randomization, 201 of the 398 patients assigned to hydroxyethyl starch 130/0.42 -- or 51% -- had died, compared with 172 of 400 patients (or 43%) assigned to Ringer's acetate.

Those numbers yielded a relative risk for death of 1.17 (95% CI 1.01 to 1.36, P=0.03).

The relative risk for the primary outcome was identical, since only one patient in each group had end-stage kidney failure and was on dialysis at the 90-day mark.

On the other hand, during the 90-day period 87 patients assigned to the starch solution -- or 22% -- were treated with renal-replacement therapy, compared with 65 (16%) of those assigned to Ringer's acetate.

Those number yielded a relative risk of 1.35 for renal-replacement therapy (95% CI 1.01 to 1.80, P=0.04).

And, 38 patients in the hydroxyethyl starch arm and 25 in the Ringer's acetate group had severe bleeding -- 10% versus 6% -- but the relative risk did not reach statistical significance.

The starch solution increased the absolute risk of death at 90 days by 8 percentage points, the researchers noted, which yields a number needed to harm of 13.

The survival curves began to separate at 20 days, Perner and colleagues reported, suggesting the difference in the primary outcome is caused by late deaths in the starch arm.

The researchers cautioned that the trial design did not include hemodynamic monitoring or co-interventions in the protocol, although participating centers were asked to follow international guidelines. "Whether this affected the results cannot be assessed," they noted.

Another limitation: the study included patients with acute kidney injury at the time of randomization, but they were equally distributed between the arms, Perner and colleagues said.

The study was supported by the Danish Research Council, the Rigshospitalet Research Council, and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

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